Pub Date : 2002-06-01DOI: 10.1161/01.HYP.0000018580.24644.18
K. Kristjánsson, A. Manolescu, A. Kristinsson, T. Hardarson, H. Knudsen, Sigurdur Ingason, G. Thorleifsson, M. Frigge, A. Kong, J. Gulcher, K. Stefánsson
We performed a genomewide scan with 904 microsatellite markers using 120 extended Icelandic families with 490 hypertensive patients. The families were identified by cross-matching a list of hypertensive patients from the Hypertension Clinic of the University Hospital (Landspitalinn) in Iceland with a genealogy database of the entire Icelandic nation. After adding 5 markers, we found linkage to chromosome 18q with an allele-sharing LOD score of 4.60 (P =2.1× 10−6). These results provide evidence for a novel susceptibility gene for essential hypertension on chromosome 18q and show that it is possible to study the genetics of essential hypertension without stratifying by subphenotypes.
{"title":"Linkage of Essential Hypertension to Chromosome 18q","authors":"K. Kristjánsson, A. Manolescu, A. Kristinsson, T. Hardarson, H. Knudsen, Sigurdur Ingason, G. Thorleifsson, M. Frigge, A. Kong, J. Gulcher, K. Stefánsson","doi":"10.1161/01.HYP.0000018580.24644.18","DOIUrl":"https://doi.org/10.1161/01.HYP.0000018580.24644.18","url":null,"abstract":"We performed a genomewide scan with 904 microsatellite markers using 120 extended Icelandic families with 490 hypertensive patients. The families were identified by cross-matching a list of hypertensive patients from the Hypertension Clinic of the University Hospital (Landspitalinn) in Iceland with a genealogy database of the entire Icelandic nation. After adding 5 markers, we found linkage to chromosome 18q with an allele-sharing LOD score of 4.60 (P =2.1× 10−6). These results provide evidence for a novel susceptibility gene for essential hypertension on chromosome 18q and show that it is possible to study the genetics of essential hypertension without stratifying by subphenotypes.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"1 1","pages":"1044-1049"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88644610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-06-01DOI: 10.1161/01.HYP.0000018040.27363.53
T. Marwick, C. Case, S. Sawada, C. Vasey, James D. Thomas
Stress echocardiography has been shown to improve the diagnosis of coronary artery disease in the presence of hypertension, but its value in prognostic evaluation is unclear. We sought to determine whether stress echocardiography could be used to predict mortality in 2363 patients with hypertension, who were followed for up to 10 years (mean 4.0±1.8) for death and revascularization. Stress echocardiograms were normal in 1483 patients (63%), 16% had resting left ventricular (LV) dysfunction alone, and 21% had ischemia. Abnormalities were confined to one territory in 489 patients (21%) and to multiple territories in 365 patients (15%). Cardiac death was less frequent among the patients able to exercise than among those undergoing dobutamine echocardiography (4% versus 7%, P < 0.001). The risk of death in patients with a negative stress echocardiogram was <1% per year. Ischemia identified by stress echocardiography was an independent predictor of mortality in those able to exercise (hazard ratio 2.21, 95% confidence intervals 1.10 to 4.43, P =0.0001) as well as those undergoing dobutamine echo (hazard ratio 2.39, 95% confidence intervals 1.53 to 3.75, P =0.0001); other predictors were age, heart failure, resting LV dysfunction, and the Duke treadmill score. In stepwise models replicating the sequence of clinical evaluation, the results of stress echocardiography added prognostic power to models based on clinical and stress-testing variables. Thus, the results of stress echocardiography are an independent predictor of cardiac death in hypertensive patients with known or suspected coronary artery disease, incremental to clinical risks and exercise results.
{"title":"Prediction of Outcomes in Hypertensive Patients With Suspected Coronary Disease","authors":"T. Marwick, C. Case, S. Sawada, C. Vasey, James D. Thomas","doi":"10.1161/01.HYP.0000018040.27363.53","DOIUrl":"https://doi.org/10.1161/01.HYP.0000018040.27363.53","url":null,"abstract":"Stress echocardiography has been shown to improve the diagnosis of coronary artery disease in the presence of hypertension, but its value in prognostic evaluation is unclear. We sought to determine whether stress echocardiography could be used to predict mortality in 2363 patients with hypertension, who were followed for up to 10 years (mean 4.0±1.8) for death and revascularization. Stress echocardiograms were normal in 1483 patients (63%), 16% had resting left ventricular (LV) dysfunction alone, and 21% had ischemia. Abnormalities were confined to one territory in 489 patients (21%) and to multiple territories in 365 patients (15%). Cardiac death was less frequent among the patients able to exercise than among those undergoing dobutamine echocardiography (4% versus 7%, P < 0.001). The risk of death in patients with a negative stress echocardiogram was <1% per year. Ischemia identified by stress echocardiography was an independent predictor of mortality in those able to exercise (hazard ratio 2.21, 95% confidence intervals 1.10 to 4.43, P =0.0001) as well as those undergoing dobutamine echo (hazard ratio 2.39, 95% confidence intervals 1.53 to 3.75, P =0.0001); other predictors were age, heart failure, resting LV dysfunction, and the Duke treadmill score. In stepwise models replicating the sequence of clinical evaluation, the results of stress echocardiography added prognostic power to models based on clinical and stress-testing variables. Thus, the results of stress echocardiography are an independent predictor of cardiac death in hypertensive patients with known or suspected coronary artery disease, incremental to clinical risks and exercise results.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"4 1","pages":"1113-1118"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81640012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-06-01DOI: 10.1161/01.HYP.0000018912.05345.55
R. de Gaudemaris, T. Lang, G. Chatellier, L. Larabi, V. Lauwers-Cances, A. Maître, E. Diène
To analyze the health disparities relative to the prevalence of arterial hypertension and its therapeutic control in the active French population, in relation to occupational categories (OC), a population of 17 359 men and 12 267 women was assessed from January 1997 to April 1998. The initial phase was a cross-sectional analysis of a cohort study designed to assess the incidence of arterial hypertension in a French working population. Information was collected by the worksite physician during the annual examination. Blood pressure (BP) was measured using a validated automatic device. Among subjects with a BP ≥140/90 mm Hg, patients not treated with antihypertensive drugs were invited to have an additional BP measurement, 1 month later. Overall prevalence was 16.1% for men and 9.4% for women. Both prevalence and therapeutic control of high BP were related to OCs in this study. Prevalence of hypertension was higher and maintenance of therapeutic control lower among lower OCs. In contrast, awareness of high BP and the proportion of hypertensive subjects under current treatment were not related to OCs. Educational level and low OC were significantly related to prevalence of high BP after adjustment for obesity, excessive alcohol consumption, and sedentary lifestyle in women only. A poor BP control under treatment was related to high alcohol intake and low OC in men. In women only, however, low educational level was related to high prevalence of hypertension and poor BP control under antihypertensive treatment. Inequalities in hypertension prevalence persist, with prevalence being higher among lower OCs. Social disparities were not observed, however, in awareness of their condition among hypertensive subjects and among patients for receiving versus not receiving any treatment for hypertension. In contrast, BP control under antihypertensive treatment was lower among lower OCs.
为了分析法国活跃人口中与职业类别(OC)相关的动脉高血压患病率及其治疗控制方面的健康差异，1997年1月至1998年4月对17 359名男性和12 267名女性进行了评估。初始阶段是一项队列研究的横断面分析，旨在评估法国工作人群中动脉高血压的发病率。信息是在年度检查时由现场医生收集的。使用经过验证的自动装置测量血压(BP)。在血压≥140/90 mm Hg的受试者中，未接受抗高血压药物治疗的患者被邀请在1个月后进行额外的血压测量。男性的总体患病率为16.1%，女性为9.4%。在本研究中，高血压的患病率和治疗控制都与OCs有关。在低oc人群中，高血压患病率较高，治疗控制维持率较低。相比之下，高血压意识和接受当前治疗的高血压患者比例与OCs无关。仅在女性中，教育水平和低OC与肥胖、过度饮酒和久坐生活方式调整后的高血压患病率显著相关。治疗期间血压控制不佳与男性高酒精摄入量和低OC有关。然而，仅在女性中，低教育水平与高血压高患病率和抗高血压治疗后血压控制不良有关。高血压患病率的不平等仍然存在，低OCs人群的患病率更高。然而，在高血压受试者和接受与未接受任何高血压治疗的患者之间，没有观察到社会差异。相比之下，低OCs患者在降压治疗下的血压控制较低。
{"title":"Socioeconomic Inequalities in Hypertension Prevalence and Care: The IHPAF Study","authors":"R. de Gaudemaris, T. Lang, G. Chatellier, L. Larabi, V. Lauwers-Cances, A. Maître, E. Diène","doi":"10.1161/01.HYP.0000018912.05345.55","DOIUrl":"https://doi.org/10.1161/01.HYP.0000018912.05345.55","url":null,"abstract":"To analyze the health disparities relative to the prevalence of arterial hypertension and its therapeutic control in the active French population, in relation to occupational categories (OC), a population of 17 359 men and 12 267 women was assessed from January 1997 to April 1998. The initial phase was a cross-sectional analysis of a cohort study designed to assess the incidence of arterial hypertension in a French working population. Information was collected by the worksite physician during the annual examination. Blood pressure (BP) was measured using a validated automatic device. Among subjects with a BP ≥140/90 mm Hg, patients not treated with antihypertensive drugs were invited to have an additional BP measurement, 1 month later. Overall prevalence was 16.1% for men and 9.4% for women. Both prevalence and therapeutic control of high BP were related to OCs in this study. Prevalence of hypertension was higher and maintenance of therapeutic control lower among lower OCs. In contrast, awareness of high BP and the proportion of hypertensive subjects under current treatment were not related to OCs. Educational level and low OC were significantly related to prevalence of high BP after adjustment for obesity, excessive alcohol consumption, and sedentary lifestyle in women only. A poor BP control under treatment was related to high alcohol intake and low OC in men. In women only, however, low educational level was related to high prevalence of hypertension and poor BP control under antihypertensive treatment. Inequalities in hypertension prevalence persist, with prevalence being higher among lower OCs. Social disparities were not observed, however, in awareness of their condition among hypertensive subjects and among patients for receiving versus not receiving any treatment for hypertension. In contrast, BP control under antihypertensive treatment was lower among lower OCs.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"4 1","pages":"1119-1125"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90501565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-06-01DOI: 10.1161/01.HYP.0000019129.44960.C0
R. Chelliah, G. Sagnella, N. Markandu, G. MacGregor
The objectives of this work were to examine the association between urinary protein and blood pressure and to compare the pattern of urinary protein excretion with essential hypertension in people of European origin (whites) and in people of African or African-Caribbean origin (blacks) living in southwest London, United Kingdom. In the groups as a whole, there were no significant differences in total urinary protein excretion between blacks and whites (geometric means [95% CI]: 94.0 [85.9 to 102.9] mg/24h for the blacks [n=151] and 102.1 [96.1 to 108.4] mg/24h for the whites [n= 219]). There were also no significant differences between blacks and whites in urinary albumin (6.5 [4.9 to 8.5] mg/24h for the blacks [n=97] and 7.1 [5.6 to 9.0] mg/24h for the whites [n=123]). In both groups, those with essential hypertension displayed a significantly raised urinary protein excretion (1.21-fold higher for the blacks and 1.19-fold higher for the whites) and albumin excretion (1.69-fold higher for the blacks and 2.40-fold higher for the whites). Urinary transferrin excretion measured in a subgroup of 67 subjects was also raised in those with essential hypertension (3.22-fold higher in the blacks and 2.76-fold higher in the whites). Examination of urinary proteins by SDS-PAGE did not identify any pattern consistent with a reduction in renal tubular protein reabsorption in those with essential hypertension. These results suggest that the increase in protein excretion in essential hypertension could be due, at least in part, to an increase in glomerular protein ultrafiltration.
{"title":"Urinary Protein and Essential Hypertension in Black and in White People","authors":"R. Chelliah, G. Sagnella, N. Markandu, G. MacGregor","doi":"10.1161/01.HYP.0000019129.44960.C0","DOIUrl":"https://doi.org/10.1161/01.HYP.0000019129.44960.C0","url":null,"abstract":"The objectives of this work were to examine the association between urinary protein and blood pressure and to compare the pattern of urinary protein excretion with essential hypertension in people of European origin (whites) and in people of African or African-Caribbean origin (blacks) living in southwest London, United Kingdom. In the groups as a whole, there were no significant differences in total urinary protein excretion between blacks and whites (geometric means [95% CI]: 94.0 [85.9 to 102.9] mg/24h for the blacks [n=151] and 102.1 [96.1 to 108.4] mg/24h for the whites [n= 219]). There were also no significant differences between blacks and whites in urinary albumin (6.5 [4.9 to 8.5] mg/24h for the blacks [n=97] and 7.1 [5.6 to 9.0] mg/24h for the whites [n=123]). In both groups, those with essential hypertension displayed a significantly raised urinary protein excretion (1.21-fold higher for the blacks and 1.19-fold higher for the whites) and albumin excretion (1.69-fold higher for the blacks and 2.40-fold higher for the whites). Urinary transferrin excretion measured in a subgroup of 67 subjects was also raised in those with essential hypertension (3.22-fold higher in the blacks and 2.76-fold higher in the whites). Examination of urinary proteins by SDS-PAGE did not identify any pattern consistent with a reduction in renal tubular protein reabsorption in those with essential hypertension. These results suggest that the increase in protein excretion in essential hypertension could be due, at least in part, to an increase in glomerular protein ultrafiltration.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"2 1","pages":"1064-1070"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88555936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-06-01DOI: 10.1161/01.HYP.0000018041.48432.B5
T. Guzik, N. West, R. Pillai, D. Taggart, K. Channon
Nitric oxide and superoxide have important roles as vascular signaling molecules. Nitric oxide (NO) reacts rapidly with superoxide, producing peroxynitrite. The relative balance between these radicals has important implications for vascular pathophysiology in hypertension and other vascular disease states. However, the relationships between superoxide, NO, and peroxynitrite formation in human blood vessels remain unclear. Accordingly, we systematically measured NO, superoxide, and peroxynitrite production from human internal mammary arteries, radial arteries, and saphenous veins from 78 patients undergoing coronary bypass surgery. Basal superoxide release was detected in all vessels at similar levels. However, endothelial removal or nitric oxide synthase inhibition increased mean superoxide release, with a corresponding reduction in peroxynitrite formation. Conversely, NO donors and superoxide scavengers both reduced superoxide release, whereas only NO donors increased peroxynitrite formation. These changes were much larger in arteries that in veins, but there were striking correlations between superoxide production, NO bioavailability, and peroxynitrite formation between the vessel types. Our findings provide direct evidence for coordinated vascular signaling mediated by interactions between NO, superoxide, and peroxynitrite and have important implications for studies of the functional effects of these radicals in human blood vessels.
{"title":"Nitric Oxide Modulates Superoxide Release and Peroxynitrite Formation in Human Blood Vessels","authors":"T. Guzik, N. West, R. Pillai, D. Taggart, K. Channon","doi":"10.1161/01.HYP.0000018041.48432.B5","DOIUrl":"https://doi.org/10.1161/01.HYP.0000018041.48432.B5","url":null,"abstract":"Nitric oxide and superoxide have important roles as vascular signaling molecules. Nitric oxide (NO) reacts rapidly with superoxide, producing peroxynitrite. The relative balance between these radicals has important implications for vascular pathophysiology in hypertension and other vascular disease states. However, the relationships between superoxide, NO, and peroxynitrite formation in human blood vessels remain unclear. Accordingly, we systematically measured NO, superoxide, and peroxynitrite production from human internal mammary arteries, radial arteries, and saphenous veins from 78 patients undergoing coronary bypass surgery. Basal superoxide release was detected in all vessels at similar levels. However, endothelial removal or nitric oxide synthase inhibition increased mean superoxide release, with a corresponding reduction in peroxynitrite formation. Conversely, NO donors and superoxide scavengers both reduced superoxide release, whereas only NO donors increased peroxynitrite formation. These changes were much larger in arteries that in veins, but there were striking correlations between superoxide production, NO bioavailability, and peroxynitrite formation between the vessel types. Our findings provide direct evidence for coordinated vascular signaling mediated by interactions between NO, superoxide, and peroxynitrite and have important implications for studies of the functional effects of these radicals in human blood vessels.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"24 1","pages":"1088-1094"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83834923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-06-01DOI: 10.1161/01.HYP.0000019128.94483.3A
A. Morrison, M. Bray, A. Folsom, E. Boerwinkle
High blood pressure is a predictor of cardiovascular disease. Hence, genes contributing to essential hypertension may play a role in the etiology of cardiovascular disease. For this reason, we examined the association between the &agr;-adducin (ADD1) G460W and G-protein &bgr;3 subunit (GNB3) 825C>T polymorphisms and the prevalence of peripheral arterial disease (PAD) and incidence of coronary heart disease (CHD) in non-Hispanic whites from the Atherosclerosis Risk in Communities (ARIC) Study. PAD prevalence was defined by an ankle-brachial index, ie, the ratio of ankle systolic blood pressure to brachial artery systolic blood pressure, of ≤0.90 for men and ≤0.85 for women. CHD incidence was determined by following the ARIC cohort for a median of 5.3 years for potential coronary events. Stratified random samples of the ARIC cohort (n=703 and n=684) were used, respectively, as the comparison groups for the PAD (n=144) and incident CHD (n=408) cases. The GNB3 825T allele and the ADD1 460W allele were not significantly associated with prevalence of PAD or incidence of CHD. However, a test of the interaction between hypertension status and the ADD1 G460W polymorphism indicated that further evaluation of the ADD1 polymorphism in only hypertensive individuals was warranted. The ADD1 460W allele was significantly associated with PAD (odds ratio [OR]: 2.61, 95% CI, 1.27–5.37, P =0.01) and CHD (hazard rate ratio [HRR]: 2.30, 95% CI, 1.20–4.42, P =0.01) in hypertensive individuals after adjustment for multiple cardiovascular disease risk factors. An interaction with hypertension in the association between the ADD1 G460W polymorphism and cardiovascular disease merits further testing in additional populations.
{"title":"ADD1 460W Allele Associated With Cardiovascular Disease in Hypertensive Individuals","authors":"A. Morrison, M. Bray, A. Folsom, E. Boerwinkle","doi":"10.1161/01.HYP.0000019128.94483.3A","DOIUrl":"https://doi.org/10.1161/01.HYP.0000019128.94483.3A","url":null,"abstract":"High blood pressure is a predictor of cardiovascular disease. Hence, genes contributing to essential hypertension may play a role in the etiology of cardiovascular disease. For this reason, we examined the association between the &agr;-adducin (ADD1) G460W and G-protein &bgr;3 subunit (GNB3) 825C>T polymorphisms and the prevalence of peripheral arterial disease (PAD) and incidence of coronary heart disease (CHD) in non-Hispanic whites from the Atherosclerosis Risk in Communities (ARIC) Study. PAD prevalence was defined by an ankle-brachial index, ie, the ratio of ankle systolic blood pressure to brachial artery systolic blood pressure, of ≤0.90 for men and ≤0.85 for women. CHD incidence was determined by following the ARIC cohort for a median of 5.3 years for potential coronary events. Stratified random samples of the ARIC cohort (n=703 and n=684) were used, respectively, as the comparison groups for the PAD (n=144) and incident CHD (n=408) cases. The GNB3 825T allele and the ADD1 460W allele were not significantly associated with prevalence of PAD or incidence of CHD. However, a test of the interaction between hypertension status and the ADD1 G460W polymorphism indicated that further evaluation of the ADD1 polymorphism in only hypertensive individuals was warranted. The ADD1 460W allele was significantly associated with PAD (odds ratio [OR]: 2.61, 95% CI, 1.27–5.37, P =0.01) and CHD (hazard rate ratio [HRR]: 2.30, 95% CI, 1.20–4.42, P =0.01) in hypertensive individuals after adjustment for multiple cardiovascular disease risk factors. An interaction with hypertension in the association between the ADD1 G460W polymorphism and cardiovascular disease merits further testing in additional populations.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"14 1","pages":"1053-1057"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77563765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-06-01DOI: 10.1161/01.HYP.0000019131.77075.54
K. Moritz, E. Wintour, M. Dodic
It has been proposed that the number of nephrons an individual has may be inversely related to his or her blood pressure. In this study using female ovine fetuses, nephron number was reduced by performing a fetal uninephrectomy during the period of active nephrogenesis (100 days of gestation, term=150 days). Lambs were born at term and grew at a similar rate. At 5 months of age, ovaries were removed and the carotid artery exteriorized into a fold of skin. Blood pressure and renal function were studied at 6 and 12 months of age. At 6 months of age, uninephrectomized lambs had significantly higher mean arterial blood pressure than sham-operated lambs (89±2 versus 82±2 mm Hg, P <0.05) when measured over a 3-day period. Heart rate was not different between the groups. Urine flow rate was similar, but glomerular filtration rate was significantly lower in uninephrectomized animals (P <0.05). Urinary concentrations and excretion rates of sodium tended to be higher in uninephrectomized animals but were similar for chloride and potassium. There was no evidence of proteinuria in the uninephrectomized lambs. Similar differences were observed in blood pressure and renal function at 12 months of age. Plasma renin concentrations at this age were lower in the uninephrectomized lambs (P <0.05). An oral salt load for 10 days did not increase blood pressure significantly in either group at 12 months of age, nor were there differences in the responsiveness to graded doses of angiotensin II. These results suggest that formation of a low nephron number in utero, may result in elevated blood pressure and compromised renal function in later life.
有人提出，一个人的肾单位数量可能与他或她的血压成反比。在本研究中，在肾形成活跃期(妊娠100天，足月=150天)进行胎儿单肾切除术，减少了雌性绵羊胎儿的肾单位数量。羔羊在足月出生，并以相似的速度生长。在5个月大时，卵巢被切除，颈动脉被外化成一层皮肤。在6个月和12个月时分别研究血压和肾功能。在6个月大时，未切除肾脏的羔羊在3天内的平均动脉血压明显高于假手术羔羊(89±2对82±2 mmhg, P <0.05)。两组之间的心率没有差异。两组尿流率相似，但肾小球滤过率明显低于未切除肾小球(P <0.05)。未切除肾的动物尿液中钠的浓度和排泄率往往更高，但氯和钾的浓度和排泄率相似。未切除肾的羔羊没有蛋白尿的迹象。在12个月大时，血压和肾功能也有类似的差异。该年龄未切除肾的羔羊血浆肾素浓度较低(P <0.05)。两组在12月龄时口服盐负荷10天没有显著升高血压，对分级剂量血管紧张素II的反应性也没有差异。这些结果表明，在子宫内形成低肾元数量，可能导致血压升高和晚年肾功能受损。
{"title":"Fetal Uninephrectomy Leads to Postnatal Hypertension and Compromised Renal Function","authors":"K. Moritz, E. Wintour, M. Dodic","doi":"10.1161/01.HYP.0000019131.77075.54","DOIUrl":"https://doi.org/10.1161/01.HYP.0000019131.77075.54","url":null,"abstract":"It has been proposed that the number of nephrons an individual has may be inversely related to his or her blood pressure. In this study using female ovine fetuses, nephron number was reduced by performing a fetal uninephrectomy during the period of active nephrogenesis (100 days of gestation, term=150 days). Lambs were born at term and grew at a similar rate. At 5 months of age, ovaries were removed and the carotid artery exteriorized into a fold of skin. Blood pressure and renal function were studied at 6 and 12 months of age. At 6 months of age, uninephrectomized lambs had significantly higher mean arterial blood pressure than sham-operated lambs (89±2 versus 82±2 mm Hg, P <0.05) when measured over a 3-day period. Heart rate was not different between the groups. Urine flow rate was similar, but glomerular filtration rate was significantly lower in uninephrectomized animals (P <0.05). Urinary concentrations and excretion rates of sodium tended to be higher in uninephrectomized animals but were similar for chloride and potassium. There was no evidence of proteinuria in the uninephrectomized lambs. Similar differences were observed in blood pressure and renal function at 12 months of age. Plasma renin concentrations at this age were lower in the uninephrectomized lambs (P <0.05). An oral salt load for 10 days did not increase blood pressure significantly in either group at 12 months of age, nor were there differences in the responsiveness to graded doses of angiotensin II. These results suggest that formation of a low nephron number in utero, may result in elevated blood pressure and compromised renal function in later life.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"112 1","pages":"1071-1076"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87680673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-06-01DOI: 10.1161/01.HYP.0000018911.46067.6E
T. Rice, T. Rankinen, Y. Chagnon, M. Province, L. Pérusse, A. Leon, J. Skinner, J. Wilmore, C. Bouchard, D. Rao
The purpose of this study was to search for genomic regions influencing resting systolic (SBP) and diastolic (DBP) blood pressure (BP) in sedentary families (baseline), and for resting BP responses (changes) resulting from a 20-week exercise training intervention (post-training–baseline) in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study. A genome-wide scan was conducted on 317 black individuals from 114 families and 519 white individuals from 99 families using a multipoint variance-components linkage model and a panel of 509 markers. Promising results were primarily, but not exclusively, found in the black families. Linkage evidence (P <0.0023) with baseline BP replicated other studies within a 1-logarithm of odds (LOD) interval on 2p14, 3p26.3, and 12q21.33, and provided new evidence on 3q28, 11q21, and 19p12. Results for several known hypertension genes were less compelling. For response BP, results were not very strong, although markers on 13q11 were mildly suggestive (P <0.01). In conclusion, these HERITAGE data, in conjunction with results from previous genomewide scans, provide a basis for planning future investigations. The major areas warranting further study involve fine mapping to narrow down 3 regions on 2q, 3p, and 12q that may contain “novel” hypertension genes, additional typing of some biological candidate genes to determine whether they are the sources of these and other signals, multilocus investigations to understand how and to what extent some of these candidates may interact, and multivariate studies to characterize any pleiotropy.
{"title":"Genomewide Linkage Scan of Resting Blood Pressure: HERITAGE Family Study","authors":"T. Rice, T. Rankinen, Y. Chagnon, M. Province, L. Pérusse, A. Leon, J. Skinner, J. Wilmore, C. Bouchard, D. Rao","doi":"10.1161/01.HYP.0000018911.46067.6E","DOIUrl":"https://doi.org/10.1161/01.HYP.0000018911.46067.6E","url":null,"abstract":"The purpose of this study was to search for genomic regions influencing resting systolic (SBP) and diastolic (DBP) blood pressure (BP) in sedentary families (baseline), and for resting BP responses (changes) resulting from a 20-week exercise training intervention (post-training–baseline) in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study. A genome-wide scan was conducted on 317 black individuals from 114 families and 519 white individuals from 99 families using a multipoint variance-components linkage model and a panel of 509 markers. Promising results were primarily, but not exclusively, found in the black families. Linkage evidence (P <0.0023) with baseline BP replicated other studies within a 1-logarithm of odds (LOD) interval on 2p14, 3p26.3, and 12q21.33, and provided new evidence on 3q28, 11q21, and 19p12. Results for several known hypertension genes were less compelling. For response BP, results were not very strong, although markers on 13q11 were mildly suggestive (P <0.01). In conclusion, these HERITAGE data, in conjunction with results from previous genomewide scans, provide a basis for planning future investigations. The major areas warranting further study involve fine mapping to narrow down 3 regions on 2q, 3p, and 12q that may contain “novel” hypertension genes, additional typing of some biological candidate genes to determine whether they are the sources of these and other signals, multilocus investigations to understand how and to what extent some of these candidates may interact, and multivariate studies to characterize any pleiotropy.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"45 1","pages":"1037-1043"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77268765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-06-01DOI: 10.1161/01.HYP.0000019130.09167.3B
X. Yi, A. Gerdes, Faqian Li
G protein–coupled receptor kinases (GRKs) are known to be involved in the development of cardiac hypertrophy. Their exact role and subcellular distribution during cardiac hypertrophy and failure remain to be elucidated. We examined expression and subcellular distribution of GRK2 and GRK5 in the left ventricle of female spontaneously hypertensive heart failure (SHHF) rats at 6 months of age using Western blots and fluorescent confocal microscopy. GRK2 was expressed mainly in the Triton X-100 soluble fraction in the left ventricle with similar expression levels between SHHF and age-matched Wistar-Kyoto (WKY) rats. GRK2 had a striated pattern which colocalized with sarcomeric &agr;-actinin and G protein in both SHHF and WKY rat myocytes and specifically accumulated in the intercalated disks of myocytes from SHHF but not WKY rats. GRK5 was expressed in both the Triton X-100 soluble fraction and Triton X-100 insoluble fraction in the left ventricle with similar expression levels between SHHF and WKY rats. GRK5 distributed diffusely in the cytoplasm in both SHHF and WKY rat myocytes and specifically accumulated in the nucleus of myocytes from SHHF but not WKY rats. GRK5 colocalized with coilin, the major component of the nuclear substructure involved in RNA synthesis and processing. The results suggest different roles for GRK2 and GRK5 in G-protein signaling and RNA biogenesis. Subcellular redistribution of GRK2 and GRK5 may be involved in cardiac hypertrophy resulting from chronic hypertension.
{"title":"Myocyte Redistribution of GRK2 and GRK5 in Hypertensive, Heart-Failure–Prone Rats","authors":"X. Yi, A. Gerdes, Faqian Li","doi":"10.1161/01.HYP.0000019130.09167.3B","DOIUrl":"https://doi.org/10.1161/01.HYP.0000019130.09167.3B","url":null,"abstract":"G protein–coupled receptor kinases (GRKs) are known to be involved in the development of cardiac hypertrophy. Their exact role and subcellular distribution during cardiac hypertrophy and failure remain to be elucidated. We examined expression and subcellular distribution of GRK2 and GRK5 in the left ventricle of female spontaneously hypertensive heart failure (SHHF) rats at 6 months of age using Western blots and fluorescent confocal microscopy. GRK2 was expressed mainly in the Triton X-100 soluble fraction in the left ventricle with similar expression levels between SHHF and age-matched Wistar-Kyoto (WKY) rats. GRK2 had a striated pattern which colocalized with sarcomeric &agr;-actinin and G protein in both SHHF and WKY rat myocytes and specifically accumulated in the intercalated disks of myocytes from SHHF but not WKY rats. GRK5 was expressed in both the Triton X-100 soluble fraction and Triton X-100 insoluble fraction in the left ventricle with similar expression levels between SHHF and WKY rats. GRK5 distributed diffusely in the cytoplasm in both SHHF and WKY rat myocytes and specifically accumulated in the nucleus of myocytes from SHHF but not WKY rats. GRK5 colocalized with coilin, the major component of the nuclear substructure involved in RNA synthesis and processing. The results suggest different roles for GRK2 and GRK5 in G-protein signaling and RNA biogenesis. Subcellular redistribution of GRK2 and GRK5 may be involved in cardiac hypertrophy resulting from chronic hypertension.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"29 1","pages":"1058-1063"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74350277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-05-01DOI: 10.1161/01.HYP.0000016179.52601.B4
Xueqing Jin, N. Fukuda, Jin-zi Su, Yimu Lai, R. Suzuki, Y. Tahira, H. Takagi, Y. Ikeda, K. Kanmatsuse, H. Miyazaki
Two distinct subtypes of angiotensin (Ang) II receptors, type 1 (AT1) and type 2 (AT2), have been identified. Vascular smooth muscle cells (VSMCs) usually express AT1 receptor. To elucidate the direct effects of the AT2 receptor on the AT1 receptor in VSMCs, we transfected AT2 receptor gene into cultured rat VSMCs. Overexpression of AT2 receptor significantly decreased expression of AT1a receptor at both the mRNA and protein levels in the presence and absence of Ang II in VSMCs. Overexpression of AT2 receptor increased expression of bradykinin and inducible NO in the presence and absence of Ang II in VSMCs. Bradykinin B2 receptor antagonist HOE–140 and NO synthase inhibitor N&ohgr;-nitro-l-arginine methyl ester (L-NAME) inhibited the decreases in AT1a receptor expression by the overexpression of AT2 receptor in VSMCs. l-Arginine augmented the decrease in AT1a receptor expression. Overexpression of AT2 receptor suppressed basal DNA synthesis and proliferation of VSMCs and abolished response of DNA synthesis to Ang II in VSMCs. Our results demonstrate that overexpression of the AT2 receptor downregulates AT1a receptor expression in rat VSMCs in a ligand-independent manner that is mediated by the bradykinin/NO pathway. Downregulation of AT1a receptor is a novel mechanism by which the AT2 receptor regulates growth and metabolism of VSMCs.
{"title":"Angiotensin II Type 2 Receptor Gene Transfer Downregulates Angiotensin II Type 1a Receptor in Vascular Smooth Muscle Cells","authors":"Xueqing Jin, N. Fukuda, Jin-zi Su, Yimu Lai, R. Suzuki, Y. Tahira, H. Takagi, Y. Ikeda, K. Kanmatsuse, H. Miyazaki","doi":"10.1161/01.HYP.0000016179.52601.B4","DOIUrl":"https://doi.org/10.1161/01.HYP.0000016179.52601.B4","url":null,"abstract":"Two distinct subtypes of angiotensin (Ang) II receptors, type 1 (AT1) and type 2 (AT2), have been identified. Vascular smooth muscle cells (VSMCs) usually express AT1 receptor. To elucidate the direct effects of the AT2 receptor on the AT1 receptor in VSMCs, we transfected AT2 receptor gene into cultured rat VSMCs. Overexpression of AT2 receptor significantly decreased expression of AT1a receptor at both the mRNA and protein levels in the presence and absence of Ang II in VSMCs. Overexpression of AT2 receptor increased expression of bradykinin and inducible NO in the presence and absence of Ang II in VSMCs. Bradykinin B2 receptor antagonist HOE–140 and NO synthase inhibitor N&ohgr;-nitro-l-arginine methyl ester (L-NAME) inhibited the decreases in AT1a receptor expression by the overexpression of AT2 receptor in VSMCs. l-Arginine augmented the decrease in AT1a receptor expression. Overexpression of AT2 receptor suppressed basal DNA synthesis and proliferation of VSMCs and abolished response of DNA synthesis to Ang II in VSMCs. Our results demonstrate that overexpression of the AT2 receptor downregulates AT1a receptor expression in rat VSMCs in a ligand-independent manner that is mediated by the bradykinin/NO pathway. Downregulation of AT1a receptor is a novel mechanism by which the AT2 receptor regulates growth and metabolism of VSMCs.","PeriodicalId":13233,"journal":{"name":"Hypertension: Journal of the American Heart Association","volume":"25 1","pages":"1021-1027"},"PeriodicalIF":0.0,"publicationDate":"2002-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78234542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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